Serum matrix metalloproteinase-2 as a prognostic marker in advanced cutaneous melanoma

The association was studied between serum concentration of matrix metalloproteinase-2 (MMP-2) and metastatic site, survival and disease progression in patients with advanced cutaneous melanoma. The patient population consisted of 50 patients who were treated with chemoimmunotherapy. The median baseline serum concentration of MMP-2 was 724 ng/ml (range 500-2297 ng/ml). There were no significant differences in MMP-2 levels according to metastatic site. Baseline MMP-2 concentration did not have a prognostic value. The patients with levels below 800 ng/ml survived for 8.8 months and those with higher levels for 9.7 months. On serial measurements, median serum MMP-2 concentration at disease progression in 25 patients was significantly higher than before treatment. Only five samples at response were available, and the levels were not significantly different from baseline levels. In conclusion, serum MMP-2 is not a prognostic marker in advanced melanoma. It also appears to be of limited clinical value in monitoring.     

The course of serum HER-2/neu levels as an independent prognostic factor for survival in metastatic breast cancer

The purpose of this study was to determine the impact of serum HER-2/neu level dynamics during the course of disease and treatment on the prognosis of patients with metastatic breast cancer. Two thousand and thirty-eight serum samples collected sequentially after disease relapse in 286 patients with metastatic breast cancer were measured by Bayer Immuno 1 trade mark assay retrospectively for serum HER-2/neu (cut-off level 15 ng/ml). One hundred and five patients (37%) presented with serum HER-2/neu continuously 相似文献   

Expression and prognostic value of matrix metalloproteinase-7 in colorectal cancer

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP- 7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p=0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test=9.957, p=0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients.     

Prognostic value of soluble P-selectin levels in colorectal cancer

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC.     

Circulating vascular endothelial growth factor six months after primary surgery as a prognostic marker in patients with colorectal cancer

High preoperative circulating vascular endothelial growth factor (VEGF) is predictive of poor prognosis in patients with colorectal cancer (CRC). However, postoperative circulating VEGF has not yet been evaluated as a prognostic marker in CRC patients. In 318 consecutive patients who had undergone curative resection of primary CRC, the prognostic value of VEGF concentrations in plasma and serum obtained 6 months postoperatively was analysed and the results compared with the prognostic value of postoperative carcinoembryonic antigen (CEA) concentrations in matched serum samples. In univariate analyses, high serum and plasma VEGF ( > 533 pg/ml and > 112 pg/ml, respectively) had no significant (p = 0.17 and p = 0.13, respectively) impact on overall survival. On the contrary, high serum CEA ( > 5 ng/ ml) was significantly (p < 0.0001) correlated to a poor prognosis. Finally, in multivariate analyses, the combination of high serum CEA and high serum VEGF was significantly (hazard ratio 3.0, p = 0.02) associated with poor survival compared to high serum CEA and low serum VEGF. It is concluded that 6 months postoperatively serum CEA is a better prognostic marker than corresponding serum and plasma VEGF. However, high serum VEGF within high serum CEA was an even better predictor of overall survival than high serum CEA alone.     

Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer.

BACKGROUND: Matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) are two proteins involved in angiogenesis. In the present study we investigated the association of pretreatment MMP-9 and VEGF serum levels with clinicopathological parameters and outcome in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From February 1998 to October 1999, pretreatment serum levels of MMP-9 and VEGF were analysed in 118 patients with enzyme-linked immunoassays. At diagnosis 50 patients (42%) were staged as early disease (I/II), 27 patients (23%) as locally advanced (IIIA/IIIB), and 41 patients (35%) had metastatic disease (IV). In 72 of the 118 patients tumours were resected and 46 patients received combination chemotherapy with gemcitabine and vinorelbine. RESULTS: The median survival of all 118 patients was 602 days. The 72 patients who had undergone surgery had a median survival of 972 days and the 46 patients who were treated with chemotherapy had a median survival of 298 days (P <0.001). Resected patients with stage I/II disease and an MMP-9 serum level 相似文献   

Serum matrix metalloproteinase-9 in head and neck squamous cell carcinoma is a prognostic marker

The aim of this study was to determine whether serum matrix metalloproteinase-9 (MMP-9) could predict cause-specific and relapse-free survival in patients with squamous cell carcinoma of head and neck. Furthermore, this study was designed to investigate whether there is an association between MMP-9 immunohistochemical staining and serum MMP-9 levels. Pretreatment serum levels of MMP-9 were quantitatively measured by ELISA assay in 67 patients presenting with a primary head and neck squamous cell carcinoma. The results were compared with the corresponding immunohistochemical staining results, clinical data and the patients' outcome. The follow-up time for all of the patients was at least 5 years. There was a statistically significant correlation between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors (p = 0.028). The cause-specific and relapse-free survival rates were clearly lower among patients with high MMP-9 serum levels (> 73 ng/ml). The 5-year cause-specific survival-rate was 40% in a patient group with high serum MMP-9, and 69% for patients with a low MMP-9 level (p = 0.027). In the same follow-up period, the cumulative relapse-free survival rate was 36% in patients presenting with a high serum MMP-9 and 66% in those with a low MMP-9 level. No correlation was found between MMP-9 serum levels and the traditional clinical or histopathologic factors. The results suggest for the first time that pretreatment serum MMP-9 level could serve as a prognostic factor in head and neck squamous cell carcinoma.     

Serum levels of matrix metalloproteinase 2 in patients with breast cancer

Matrix metalloproteinases (MMPs) have been reported to be associated with invasive and metastatic behaviors of human malignant tumors. However, there is still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating MMP-2 and breast cancer. Fifty-seven consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumor (six with fibrocystic disease and six with fibroadenoma). Serum concentrations of MMP-2 were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor stage, age, estrogen receptor, lymph node status, and TNM staging were reviewed and recorded. The mean value of serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and those of control group were 593.3+/-134.0 ng/ml and the difference was significant (P=0.026). Furthermore, there were significantly higher serum levels of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in the patients with more advanced lymph node status(P=0.011) and in the patients with more advanced TNM staging (P<0.001). In multivariate analysis, TNM staging (P<0.001) appeared as independent factor regarding the significant higher serum levels of MMP-2. Patients with more advanced TNM staging were shown to have higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the severity of invasive breast cancer and deserve further evaluation.     

Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)

PURPOSE: In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. RESULTS: Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level (P=0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. CONCLUSIONS: The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.     

Tissue MMP-2 and MMP-9 [corrected] are better prognostic factors than serum MMP-2/TIMP-2--complex or TIMP-1 [corrected] in stage [corrected] I-III lung carcinoma

Matrix metalloproteinases (MMPs) are involved in tumor growth and spreading. Here, we investigated the tumor immunoreactive protein of MMP-2, MMP-9 and TIMP-1 as well as the levels of circulating total TIMP-1 and MMP-2/TIMP-2-complex as prognostic factors in lung cancer patients. The material included 59 patients, 30 with a squamous cell carcinoma, 21 with an adenocarcinoma and eight with other histology. Circulating antigens were measured by ELISA assay and the protein expression in primary tumors was analyzed by streptavidin-biotin immunohistochemical staining using specific monoclonal antibodies. The strong positivity for MMP-2 or MMP-9 in tumor predicted poor prognosis. The 5-year survival rates were 83 or 85% in patients negative for MMP-2 or MMP-9, respectively. Only 17% of the patients with a tumor highly positive for MMP-2 and 43% of those with a high positivity for MMP-9 survived at that time (Cox regression P=0.042 for MMP-2 and log rank P=0.046 for MMP-9). On the contrary, strong tissue positivity for TIMP-1 demonstrated a tendency for a favorable survival, although the difference did not reach statistical significance. In patients with a squamous cell carcinoma Stage I, low serum TIMP-1 (or=300 ng/ml) associated with an increased survival rate, the 5-year survival being 81 versus 34% (log rank P=0.069) in patients with high or low serum levels for MMP-2/TIMP-2-complex, respectively. Tissue MMP-2 correlated to high expression of MMP-9 immunoreactive protein (P=0.003), but the serum levels of MMP-2/TIMP-2-complex or TIMP-1 did not correlate to the immunostaining of the corresponding tumors. We conclude that in lung carcinoma the best prognostic value is achieved by using immunohistochemistry for MMP-2 and MMP-9. In early disease, however, serum TIMP-1 or MMP-2/TIMP-2-complex could offer some further prognostic value.     

Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease.

In this study, our aim was to investigate the impact of various prognostic factors on survival in patients with pancreatic carcinoma. The group consisted of 127 cases with adenocarcinoma histologically. The patients had a median age of 58 years, and 81 (64%) were male. The median survival time of the whole group was 7 months, and the 4-year survival rate was 18%. The median survival duration of the patients without metastases was 8 months, and the survival rate at 1 year was 37.5% and 7.2% at 5 years. It was associated with improved survival compared with the cases with metastatic disease (p < 0.0001). In univariate analysis, decreased performance status (p = 0.0009) and unresectability of tumor (p < 0.0001) were associated with poor outcome. However, only surgery was found to be a statistically significant parameter in multivariate analysis (p = 0.002). The median survival duration of patients with metastases was 5 months, and the 1-year survival rate was 10%. Age younger than 60 years (p = 0.04), decreased serum hemoglobin levels (p = 0.04), and elevated lactic dehydrogenase (LDH) levels (p = 0.0001) were associated with a significantly shorter survival rate. In the Cox model, a high serum LDH level was the only independent unfavorable prognostic factor (p = 0.001). In conclusion, surgical intervention in the group without metastases and serum LDH levels in the group with metastases were the most important prognostic factors influencing survival. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced pancreatic cancer.     

High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma.

PURPOSE: Matrix metalloproteinases (MMP) are proteolytic enzymes that play an important role in various aspects of cancer progression. In the present work, we have studied the prognostic significance of serum levels of gelatinase B (MMP-9), collagenase-1 (MMP-1), and collagenase-3 (MMP-13) in patients with advanced melanoma. EXPERIMENTAL DESIGN: Total pretreatment serum levels of MMP-9 in 71 patients and MMP-1 and MMP-13 in 48 patients were determined by an assay system based on ELISA. Total MMP levels were also assessed in eight healthy controls. The active and latent forms of MMPs were defined by using Western blot analysis and gelatin zymography. RESULTS: Patients with high serum levels of MMP-9 (> or = 376.6 ng/mL; n = 19) had significantly poorer overall survival (OS) than patients with lower serum MMP-9 levels (n = 52; median OS, 29.1 versus 45.2 months; P = 0.033). High MMP-9 levels were also associated with visceral or bone metastasis (P = 0.027), elevated serum alkaline phosphatase level (P = 0.0009), and presence of liver metastases (P = 0.032). Serum levels of MMP-1 and MMP-13 did not correlate with OS. MMP-1 and MMP-9 were found mainly in latent forms in serum, whereas the majority of MMP-13 in serum was active (48 kDa) form. MMP-13 was found more often in active form in patients (mean, 99% of the total MMP-13 level) than in controls (mean, 84% of the total MMP-13 level; P < 0.0001). After initiating the therapy, patients with elevated levels of MMP-1 (> or = 29.8 ng/mL, n = 10) progressed more rapidly than patients with lower levels (median, 1.9 versus 3.5 months; P = 0.023). Serum levels of MMP-9 and MMP-13 did not correlate with the time to progression (TTP). In multivariate analysis with age and gender, MMP-9 or MMP-1 turned out to be independent prognostic factors for OS [P = 0.039; hazard ratio (HR), 1.8; 95% confidence interval (95% CI), 1.03-3.3] or TTP (P = 0.023; HR, 2.7; 95% CI, 1.15-6.4), respectively. CONCLUSIONS: Our findings provide evidence that MMP-1, MMP-9, and MMP-13 play important roles at different phases of metastatic melanoma spread and that serum MMP-9, in particular, could have clinical value in identifying patients at high risk for melanoma progression.     

Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients.

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.     

β6-integrin serves as a novel serum tumor marker for colorectal carcinoma

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β₆-integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.     

Serum c-erbB-2 protein is a useful marker for monitoring tumor recurrence of the breast

C-erbB-2 oncogene protein (ErbB-2/HER-2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB-2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I-IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty-nine patients (34%) had higher preoperative serum ErbB-2 levels (>or=5.4 ng/ml). A higher preoperative serum ErbB-2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB-2. Seventeen patients died of tumor progression. The recurrence-free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB-2 and 41% in 29 patients with a higher preoperative serum ErbB-2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB-2 was an independent prognostic factor for recurrence-free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15-3 and ErbB-2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast.     

Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease.

AIMS: The degradation of the extracellular matrix is intrinsic to the invasion and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their natural inhibitors are involved in this process. The study aims to investigate if plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be useful markers in the diagnosis and prognosis of colorectal cancer (CRC) metastatic liver disease. METHODS: Fifty-seven patients undergoing liver metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma levels were determined by zymography and ELISA, before and after the resection of liver metastases. Data were compared with those of healthy controls (n=51) and primary CRC patients (n=94). The diagnostic and prognostic potential was investigated with ROC-curves and Kaplan-Meier survival analysis. RESULTS: Plasma proMMP-2 levels were lower (P<0.001), and TIMP-1 levels higher (P<0.001) in CRC metastatic liver disease than in healthy controls. If compared to those in primary CRC patients, no differences were found. In ROC-curves, the area under the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, -9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and prognostic examinations, CEA proved to be a better marker. In the postoperative follow-up, protracted low levels of proMMP-2 seemed related to disease recurrence. CONCLUSION: The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.     

Serum matrix metalloproteinase-8 is associated with ulceration and vascular invasion of malignant melanoma

Serological markers of malignant melanoma have failed to provide prognostic significance in patients who are tumour-free after surgery. Immune response regulation is important regarding progression and therapeutic interventions of malignant melanoma. Matrix metalloproteinase (MMP)-8 is one of the collagenases involved in the regulation of tissue remodelling and immune response, being incompletely studied in melanoma as yet. We assessed whether serum MMP-8 is of prognostic value in malignant melanoma. We studied serum samples of 117 patients, of which 63 were stage I, 13 stage II, 12 stage III and 29 stage IV. The mean serum MMP-8 levels (47.5 ng/ml) did not significantly correlate with patient or tumour characteristics, that is, patient sex, age, tumour Clark's or Breslow's classification, sentinel lymph node status or to survival. Importantly, high serum MMP-8 levels were significantly related to presence of vascular invasion (P=0.001) in primary tumour, tumour ulceration (P=0.003) and tumour bleeding (P=0.033). Tendency to increased serum MMP-8 levels in patients with coronary heart disease or type II diabetes mellitus was detected. These data imply that high serum MMP-8 level is associated with earlier recognized histopathology markers of melanoma progression. Results also suggest that elevated serum MMP-8 might be related to haematogenous spreading of melanoma through vascular invasion.     

Clinicopathologic significance of plasma matrix metalloproteinase-2 and -9 levels in patients with undifferentiated nasopharyngeal carcinoma.

Increased in plasma pro-MMP2 and pro-MMP9 levels in patients with advanced stage NPC were observed. Plasma pro-MMP2 is a significant independent prognostic marker for undifferentiated NPC. AIM: Upregulation of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) expression is observed in many cancers and high level of these proteins are found in peripheral blood of many cancer patients. In this study, we aimed at evaluating the plasma pro-MMP2 and pro-MMP9 pro-enzymes (pro-MMP2 and pro-MMP9) levels and their clinical significances in patients with undifferentiated nasopharyngeal carcinoma (NPC). METHODS: The plasma pro-MMP2 and pro-MMP9 levels were measured in 40 NPC patients and 40 normal individuals by enzyme linked immunosorbant assay. RESULTS: By using the Cox-regression model, a high pro-MMP2 level was found to be significantly correlated with poorer survival. Patients with plasma pro-MMP2 below 650 ng/ml had higher 5-year survival rate of 89%, compared with 50% for patients with plasma pro-MMP2 above 650 ng/ml. CONCLUSIONS: A high level of plasma pro-MMP2 was associated with poor survival of NPC patients independent of sex, age and stage.